Can β-cells be derived from exocrine pancreas?

被引:37
作者
Baeyens, L. [1 ]
Bouwens, L. [1 ]
机构
[1] Free Univ Brussels, Vrije Univ Brussel, Diabet Res Ctr, Cell Differentiat Unit, B-1090 Brussels, Belgium
关键词
islets of Langerhans; regeneration; roprogramming; stem cells; transdifferentiation;
D O I
10.1111/j.1463-1326.2008.00949.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A major goal of research aiming at improving islet cell replacement therapy is to find the most Suitable progenitor cell type, from which functional beta-cells call be generated in large numbers, Many possibilities have been raised, including beta-cells themselves, embryonic or adult stem cells and reprogramming of other cell types. Sonic of these progenitor types may be active or reside in a dormant state in adults in vivo, while others call be rather considered to be products of tissue engineering in vitro. Starting from the available pancreas organs from cadaveric donors, all attractive possibilily is to reprogram acinar exocrine cells into beta-cells. Indeed, acinar cells isolated from adult rat display a pronounced plasticity in culture. After an initial step of dedifferentiation, they can be redirected to the beta-cell phenotype by adding agonists of the JAK2/STAT3 signalling, pathway to the medium epidermal growth Factor and eleukaemia inhibitory factor). The acinar cells that undergo exocicrine-to-endocrine trans differeniatio first need to re-express neurogenin-3 and then need to escape inhibition by Notch signalling. The insulin-expressing cells that are generated in this way are glucose-regulated and call normalize glycaemia after transplantation into diabetic immunocompromised mice. It will now be important to translate these findings to human cells.
引用
收藏
页码:170 / 178
页数:9
相关论文
共 75 条
[51]   Expansion and redifferentiation of adult human pancreatic islet cells [J].
Ouziel-Yahalom, L ;
Zalzman, M ;
Anker-Kitai, L ;
Knoller, S ;
Bar, Y ;
Glandt, M ;
Herold, K ;
Efrat, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 341 (02) :291-298
[52]   Proliferation of sorted human and rat beta cells [J].
Parnaud, G. ;
Bosco, D. ;
Berney, T. ;
Pattou, F. ;
Kerr-Conte, J. ;
Donath, M. Y. ;
Bruun, C. ;
Mandrup-Poulsen, T. ;
Billestrup, N. ;
Halban, P. A. .
DIABETOLOGIA, 2008, 51 (01) :91-100
[53]  
Plachot C, 2001, HISTOCHEM CELL BIOL, V116, P131
[54]  
Ramiya VK, 2000, NAT MED, V6, P278
[55]   Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro [J].
Rooman, I ;
Heremans, Y ;
Heimberg, H ;
Bouwens, L .
DIABETOLOGIA, 2000, 43 (07) :907-+
[56]   Combined gastrin and epidermal growth factor treatment induces islet regeneration and restores normoglycaemia in C57Bl6/J mice treated with alloxan [J].
Rooman, I ;
Bouwens, L .
DIABETOLOGIA, 2004, 47 (02) :259-265
[57]   Gastrin stimulates β-cell neogenesis and increases islet mass from transdifferentiated but not from normal exocrine pancreas tissue [J].
Rooman, I ;
Lardon, J ;
Bouwens, L .
DIABETES, 2002, 51 (03) :686-690
[58]   Mitogenic effect of gastrin and expression of gastrin receptors in duct-like cells of rat pancreas [J].
Rooman, I ;
Lardon, J ;
Flamez, D ;
Schuit, F ;
Bouwens, L .
GASTROENTEROLOGY, 2001, 121 (04) :940-949
[59]   Expression of the notch signaling pathway and effect on exocrine cell proliferation in adult rat pancreas [J].
Rooman, Ilse ;
De Medts, Nele ;
Baeyens, Luc ;
Lardon, Jessy ;
De Breuck, Saskia ;
Heimberg, Harry ;
Bouwens, Luc .
AMERICAN JOURNAL OF PATHOLOGY, 2006, 169 (04) :1206-1214
[60]   Clinical outcomes and insulin secretion after islet transplantation with the edmonton protocol [J].
Ryan, EA ;
Lakey, JRT ;
Rajotte, RV ;
Korbutt, GS ;
Kin, T ;
Imes, S ;
Rabinovitch, A ;
Elliott, JF ;
Bigam, D ;
Kneteman, NM ;
Wanock, GL ;
Larsen, I ;
Shapiro, AMJ .
DIABETES, 2001, 50 (04) :710-719